This study aims to evaluate whether adding celecoxib to standard therapy can improve clinical outcomes in patients with advanced intrahepatic cholangiocarcinoma. The current standard treatment typically consists of immunotherapy combined with chemotherapy; however, there are significant inter-patient differences in treatment response. Therefore, this study further introduces the biomarker CK5/6 to identify patient subgroups who are more likely to benefit, thereby exploring a more precise therapeutic strategy.
All eligible participants will be randomly assigned after enrollment to either the control group or the experimental group. The control group will receive the current standard first-line regimen, which includes the immunotherapy agent pembrolizumab combined with the chemotherapy agents gemcitabine and cisplatin. The experimental group will receive the same standard treatment, with the addition of oral anti-inflammatory therapy with celecoxib taken twice daily throughout the entire treatment period.
Each treatment cycle lasts 21 days. During treatment, patients will undergo regular imaging assessments, laboratory tests, and safety evaluations to monitor tumor response and treatment-related adverse events, and will be followed until disease progression or discontinuation of treatment. In addition, blood and tissue samples will be collected during the study to investigate tumor biology and potential predictive biomarkers.
The primary endpoints of this study include progression-free survival and objective response rate, along with concurrent safety evaluation. Adverse events potentially associated with chemotherapy, immunotherapy, and celecoxib may occur, such as bone marrow suppression, gastrointestinal reactions, immune-related inflammatory responses, as well as renal or cardiovascular toxicities. The study team will closely monitor and promptly manage all adverse events.
This study aims to explore a CK5/6-based stratified personalized combination therapy strategy, with the goal of improving treatment benefit in patients with advanced intrahepatic cholangiocarcinoma and providing evidence for optimizing future clinical treatment strategies.
Age ≥ 18 years.
Histologically or cytologically confirmed intrahepatic cholangiocarcinoma (iCCA).
Unresectable locally advanced, recurrent, or metastatic disease.
No prior systemic therapy for advanced disease.
Other primary malignancies including extrahepatic cholangiocarcinoma, gallbladder carcinoma, or ampullary carcinoma.
CK5/6 H-score < 1.0.
Prior systemic therapy for advanced or metastatic disease.
Active gastrointestinal bleeding, peptic ulcer disease, or high risk of gastrointestinal perforation.
Parallel
Celecoxib + Pembrolizumab + Gemcitabine/Cisplatin
DrugCelecoxib is administered orally at a dose of 200 mg twice daily continuously in the experimental arm. Treatment is initiated at Cycle 1 Day -7 and continued until disease progression, unacceptable toxicity, or withdrawal.
Pembrolizumab + Gemcitabine/Cisplatin
DrugParticipants receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle in combination with gemcitabine 1000 mg/m² and cisplatin 25 mg/m² administered intravenously on Days 1 and 8 of each cycle. Cisplatin is administered for up to 8 cycles. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from randomization to the first documented disease progression per RECIST v1.1 criteria or death from any cause, whichever occurs first. Disease progression will be assessed by imaging review according to RECIST v1.1 in both treatment arms.
Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by investigators according to RECIST v1.1 criteria in both treatment arms.
Disease Control Rate (DCR)
Disease control rate is defined as the proportion of participants achieving complete response, partial response, or stable disease according to RECIST v1.1 criteria.
Overall Survival (OS)
Overall survival is defined as the time from randomization to death from any cause.
Duration of Response (DoR)
Duration of response is defined as the time from first documented objective response (CR or PR) to disease progression or death.
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Shanghai 6th People's Hospital
Lead sponsor
RenJi Hospital
Sponsor institution
Shanghai 10th People's Hospital
Collaborator
Wuhan TongJi Hospital
Collaborator
Sun Yat-Sen University Cancer Center
Collaborator
RenJi Hospital
Collaborator
